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PMID: 11522818 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated by glucocorticoids and liver-enriched transcription factors.

Nucleic acids research ·Vol. 29 ·No. 17 ·2001-09-01 ·Pages 3495-505

Bailly A, Torres-Padilla ME, Tinel AP, Weiss MC

Abstract

We have characterized a 700 bp enhancer element around -6 kb relative to the HNF4alpha1 transcription start. This element increases activity and confers glucocorticoid induction to a heterologous as well as the homologous promoters in differentiated hepatoma cells and is transactivated by HNF4alpha1, HNF4alpha7, HNF1alpha and HNF1beta in dedifferentiated hepatoma cells. A 240 bp sub-region conserves basal and hormone-induced enhancer activity. It contains HNF1, HNF4, HNF3 and C/EBP binding sites as shown by DNase I footprinting and electrophoretic mobility shift assays using nuclear extracts and/or recombinant HNF1alpha and HNF4alpha1. Mutation analyses showed that the HNF1 site is essential for HNF1alpha transactivation and is required for full basal enhancer activity, as is the C/EBP site. Glucocorticoid response element consensus sites which overlap the C/EBP, HNF4 and HNF3 sites are crucial for optimal hormonal induction. We present a model that accounts for weak expression of HNF4alpha1 in the embryonic liver and strong expression in the newborn/adult liver via the binding sites identified in the enhancer.

MeSH Terms
Animals Base Sequence Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Binding Sites/genetics CCAAT-Enhancer-Binding Protein-alpha/metabolism Chloramphenicol O-Acetyltransferase/genetics,metabolism DNA-Binding Proteins/metabolism Dexamethasone/pharmacology Enhancer Elements, Genetic/genetics,physiology Gene Expression Regulation/drug effects Glucocorticoids/pharmacology Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 1-beta Hepatocyte Nuclear Factor 3-alpha Hepatocyte Nuclear Factor 4 Liver/metabolism Luciferases/genetics,metabolism Mice Molecular Sequence Data Nuclear Proteins/metabolism Phosphoproteins/genetics,metabolism Plasmids/genetics Promoter Regions, Genetic/genetics Protein Binding Recombinant Fusion Proteins/genetics,metabolism Regulatory Sequences, Nucleic Acid/genetics,physiology Transcription Factors/genetics,metabolism,physiology Transcription, Genetic Tumor Cells, Cultured
Chemicals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors CCAAT-Enhancer-Binding Protein-alpha DNA-Binding Proteins Foxa1 protein, mouse Glucocorticoids Hepatocyte Nuclear Factor 1-alpha Hepatocyte Nuclear Factor 3-alpha Hepatocyte Nuclear Factor 4 Hnf1a protein, mouse Hnf1b protein, mouse Nuclear Proteins Phosphoproteins Recombinant Fusion Proteins Tcfl4 protein, mouse Transcription Factors Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factor 1-beta Dexamethasone Luciferases Chloramphenicol O-Acetyltransferase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Bailly A
Unité de Génétique de la Différenciation, FRE 2364 du CNRS, Institut Pasteur, 25 Rue du Dr Roux, 75724 Paris Cedex 15, France.
Torres-Padilla M E
Tinel A P
Weiss M C
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
1362-4962
DOI
10.1093/nar/29.17.3495
Published
2001-09-01
Pages
3495-505
Language
English
Region
England
NLM ID
0411011
PMCID
PMC55877
Subset
IM
Databases
GENBANK
AF320052
External Links
PubMed source DOI: 10.1093/nar/29.17.3495 PMC Full Text View journal details
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